C57BL/6-Xpr1^tm1.1Frsv/J

Stock number: 037220
Product name: Xpr1^lox
Research areas: Research Tools

Description

Xpr1^lox conditional mutant mice possess loxP sites flanking exon 2 of the Xpr1 (xenotropic and polytropic retrovirus receptor 1) gene and may be useful in generating conditional mutations to study inorganic phosphate (Pi) regulation and bone and kidney disorders.

Detailed description

Xpr1 (xenotropic and polytropic retrovirus receptor 1) encodes a G-protein coupled receptor involved in the regulation of inorganic phosphate (Pi) specifically in Pi transport. The conditional Xpr1^lox mice possess loxP sites flanking exon 2. Xpr1 expression is not altered. Mice homozygous for the mutation are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in cre-expressing tissues. Deletion of exon 2 is expected to result in a null allele that abolishes Xpr1 expression in a tissue-specific manner. Germline deletion of Xpr1 results in embryonic lethality.

For example, when bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element (TRE; tetO) and a reverse tetracycline-controlled transactivator protein under the control of the murine Pax8 promoter (Tg(Pax8-rtTA2S*M2)1Koes, Stock No. 007176, triple mutant progeny treated with doxycycline exhibit impaired renal Pi efflux, proximal renal tubule dysfunction (similar to Fanconi syndrome), and hypophosphatemic rickets. The Pax8 promoter directs expression to proximal and distal tubules and the collecting duct system of both embryonic and adult kidney.

Development

The Xpr1^lox targeting construct contains a loxP site upstream of exon 2 and a second loxP site downstream of exon 2 in the mouse Xpr1 locus on chromosome 17. The construct also includes an FRT-flanked neomycin cassette, which is removed with a self-excising flp recombinase included in the construct. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were bred to C57BL/6 female mice and maintained on the C57BL/6 background by the donating laboratory (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

In 2022, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. One of the 43 markers throughout the genome was segregating with an unknown source on Chromosome 12. Also, 2 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Xpr1^tm1.1Frsv
Name: targeted mutation 1, Dmitri Firsov
MGI accession ID: MGI:7261304
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Xpr1^lox
Marker symbol: Xpr1
Marker name: xenotropic and polytropic retrovirus receptor 1
Marker synonyms: IBGC6; Rmc1; Rmc-1; SLC53A1; suppressor of yeast G^a deletion; Syg1; X3
Chromosome: 1
Strain of origin: C57BL/6
Molecular note: The targeting construct contains a loxP site upstream of exon 2 and a second loxP site downstream of exon 2. The construct also includes an FRT-flanked neomycin cassette, which is removed with a self-excising flp recombinase included in the construct.